Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell RNA-seq analysis of young (2 months) and old (18 months) mouse hematopoietic stem and progenitor cells

ABSTRACT: Hematopoietic stem cells (HSCs) represent a rare population of cells residing in the Bone Marrow (BM) at the top of hematopoietic hierarchy. A critical balance is maintained between self-renewal and lineage differentiation of HSCs to maintain hematopoietic homeostasis. With aging, this balance is altered with an increase of self-renewal long term HSCs and a myeloid biased differentiation, which favors the appearance of myeloid leukemias and anemias. This experiment aims to understand molecular mechanisms that cause this aged-related disequilibrium in the mouse. To this end, we generated single cell RNA-seq data from pools of young and old hematopoietic stem and progenitor cells (HSPCs), isolated from mouse BMs.

ORGANISM(S): Mus musculus

PROVIDER: GSE147729 | GEO | 2021/02/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Igf2bp2 deletion reduces energy metabolism, gIgf2bp2 deletion reduces energy metabolism, growth signaling, and aging of hematopoietic stem cells in micerowth signaling, and aging of hematopoietic stem cells in mice

Project description:Increasing evidence links metabolic activity and cell growth to decline in hematopoietic stem cell (HSC) function during aging. The Lin28b/Hmga2 pathway controls tissue development and in the hematopoietic system the postnatal downregulation of this pathway causes a decrease in self renewal of adult HSCs compared to fetal HSCs. Igf2bp2 is an RNA binding protein and a mediator of the Lin28b/Hmga2 pathway, which regulates metabolism and growth signaling by influencing RNA stability and translation of its target genes. It is currently unknown whether Lin28/Hmga2/Igf2bp2 signaling impacts on aging-associated impairments in HSC function and hematopoiesis. Here, we analyzed homozygous Igf2bp2 germline knockout mice and wildtype control animals to address this question. The study shows that Igf2bp2 deletion rescues aging phenotypes of the hematopoietic system, such as the expansion of HSC numbers in bone marrow and the biased increase of myeloid cells in peripheral blood. This rescue of hematopoietic aging coincides with reduced mitochondrial metabolism and glycolysis in Igf2bp2-/- HSCs compared to Igf2bp2+/+ HSCs. Conversely, Igf2bp2 overexpression activates protein synthesis pathways in HSCs and leads to a rapid loss of self renewal by enhancing myeloid skewed differentiation in an mTOR/PI3K-dependent manner. Together, these results show that Igf2bp2 regulates energy metabolism and growth signaling in HSCs and that the activity of this pathways influences self renewal, differentiation, and aging of HSCs.

2024-05-21 | PXD018535 | Pride

Rad21-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation

Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.

2018-11-28 | PXD011537 | Pride

Human hematopoietic stem cell expansion through modulation of lineage-associated gene expression programs

Project description:Hematopoietic stem cells (HSCs) must balance self-renewal and lineage differentiation to regenerate the hematopoietic system throughout life. HSCs exhibit lineage-associated gene expression that keeps them responsive to demands of mature blood production. However, it is not known whether this process, termed lineage priming, directly influences HSC self-renewal. We investigated the link between stemness and lineage priming by attenuating the early lymphoid transcription factor E47 through ID2 over-expression (OE). Transcriptional profiling of ID2 OE HSCs showed down regulation of B-cell factors including EBF1 and FOXO1 with a concomitant increase in stemness programs and myeloerythroid factors including CEBPA and GATA1. This resulted in myeloid commitment bias from the earliest stages of differentiation. HSC self-renewal was strongly affected by this lineage perturbation resulting in an 11-fold expansion of HSCs. Thus, early lymphoid transcription factors antagonize human HSC self-renewal, providing a direct link between differentiation program priming and the maintenance of stem cell self-renewal. Three independent lineage depleted CB samples were transduced with P-CTRL or P-ID2 and injected into 5 mice (30 mice total). From every group of 5 mice, human lin- cells were isolated and GFP+CD34+CD38-CD45RA- HSPCs were sorted by FACS.

2013-12-01 | E-GEOD-45486 | biostudies-arrayexpress

Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion

2013-12-01 | GSE45486 | GEO

Regulatory Role of S100A6 in Hematopoetic Stem Cells

Project description:The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration and apoptosis, but the interaction between intracellular Ca2+ and cytoplasmic chaperon protein in regulating fate options of long term-HSCs (LT-HSC) is unknown. We created a S100A6 conditional knockout mouse model in the hematopoietic system and our studies showed that in S100A6KO, the number of LT-HSCs was significantly reduced and HSCs engrafted poorly. After 5FU challenge, the frequency of S100A6KO HSCs remained significantly low. Our data showed that S100A6 failed to self-renew through Akt pathway in an intracellular calcium (Cai2+)-dependent manner. Expression profiling of S100A6KO obtained from gene signatures revealed that cytosolic calcium level and proteins translocation to mitochondria were decreased. Mitochondrial oxidative phosphorylation was impaired in S100A6KO. Proteomic data indicated Hsp90 protein and chaperonin family were reduced. Our findings demonstrated that S100A6 regulates fate options of HSCs self-renewal through integrating Akt signaling, specifically governing mitochondria metabolic function and protein quality.

2020-06-22 | PXD015854 | Pride

MicroRNA array analysis of Pbx1-deficient and control murine HSCs and Flk2neg MPPs

Project description:The balance of self-renewal and differentiation is crucial to ensure the homeostasis of the hematopoietic system, and is a key hallmark of hematopoietic stem cells (HSCs); however, the underlying molecular pathways are not completely understood, including the role of micro-RNAs. To assess micro-RNA contributions, we performed micro-RNA profiling of HSCs and their immediate downstream progeny multi-potent progenitors (MPPs) from wild type control and Pbx1-conditional knockout mice, whose HSCs display a profound self-renewal defect.

2019-04-01 | GSE113062 | GEO

Characterisation of the myeloid differentiation process of human hematopoietic stem cells

Project description:Hematopoietic stem cells (HSCs) can self-renew and/or differentiate into various functionally divergent progenitor cell types, such as common myeloid progenitors (CMPs), megakaryocyte-erythrocyte progenitors (MEPs) or granulocyte-macrophage progenitors (GMPs). When the process of self-renewal and differentiation is altered, e.g. upon genetic or epigenetic changes in HSCs, abnormal (pre)leukemic stem cell subpopulations may form, eventually resulting in the onset of hematological malignancies. To gain insight into the physiology and subsequent patho-physiology of self-renewal and differentiation, we performed RNA sequencing as well as proteomics analyses of human HSCs and downstream (myeloid) progenitor cells.

2019-04-16 | GSE113182 | GEO

miR-125a Confers Multi-Lineage Long-Term Repopulating Stem Cell Activity to Murine and Human Hematopoietic Progenitors

Project description:Umbilical cord blood (CB) is a non-invasive, convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. One feasible option would be to expand HSCs to improve therapeutic outcome, however available protocols and the molecular mechanisms governing the self-renewal of HSC are unclear. Here we show that ectopic expression of a single miRNA, miR-125a, in purified murine and human multipotent progenitors (MPP) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and Western blot analysis, we identified a restricted set of miR-125a targets which revealed the involvement of the MAP kinase signaling pathway in conferring long-term repopulating capacity to multipotent progenitors in human and mice. Our findings offer the innovative potential to use MPP with enhanced self-renewal activity to augment limited sources of HSC to improve clinical protocols.

2017-01-11 | PXD003931 | Pride

Global Gene Expression of hematopoietic stem cells expressing endogenous NrasG12D/G12D, NrasG12D/+, Nras+/+

Project description:Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (NrasG12D/+) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of NrasG12D/+ in a pure C57BL/6 background does not induce hyperactivated GM-CSF signaling or increased proliferation in myeloid progenitors. It is thus unclear how NrasG12D/+ signaling promotes leukemogenesis. Here we show that hematopoietic stem cells (HSCs) expressing NrasG12D/+ serve as MPN initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant NrasG12D/+ HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacological and genetic approaches attenuates the cycling of NrasG12D/+ HSCs and prevents the expansion of NrasG12D/+ HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis. three NrasG12D/G12D HSCs samples, three NrasG12D/+ HSCs samples, two Nras+/+ HSCs control samples.

2013-05-29 | E-GEOD-46948 | biostudies-arrayexpress

Gene expression signatures of Meis1 conditional knockout hematopoietic stem cells

Project description:Meis1 encodes a TALE family homeodomain protein that was first identified as a common retroviral integration site in mouse BHX2 myeloid leukemia. It functions as a DNA binding co-factor of Hox proteins through interacting with Pbx, a member of another TALE family protein. Moreover, Meis1 homozygous knockout mice are embryonic lethal, showing significant defects in vasculogenesis, eye development and hematopoiesis. Severe defects were also observed in adult hematopoiesis by conditional inactivation of Meis1 in vivo. Meis1 is critical to maintain the balance between enter and exit from cell cycles of hematopoietic stem cells (HSCs), indicating that Meis1 regulates self-renewal and quiescence of HSCs. Total RNA was isolated from KSL cells obtained from poly(I:C)-treated Mx1-Cre Meis1fl/fl and sham-treated Meis1fl/fl mice.

2013-12-01 | E-GEOD-38336 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data